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  1. Article ; Online: Harnessing Whole Genome Polygenic Risk Scores to Stratify Individuals Based on Cardiometabolic Risk Factors and Biomarkers at Age 10 in the Lifecourse-Brief Report.

    Richardson, Tom G / O'Nunain, Katie / Relton, Caroline L / Davey Smith, George

    Arteriosclerosis, thrombosis, and vascular biology

    2022  Volume 42, Issue 3, Page(s) 362–365

    Abstract: Background: In this study, we investigated the capability of polygenic risk scores to stratify a cohort of young individuals into risk deciles based on 10 different cardiovascular traits and circulating biomarkers.: Methods: We first conducted large- ... ...

    Abstract Background: In this study, we investigated the capability of polygenic risk scores to stratify a cohort of young individuals into risk deciles based on 10 different cardiovascular traits and circulating biomarkers.
    Methods: We first conducted large-scale genome-wide association studies using data on adults (mean age 56.5 years) enrolled in the UK Biobank study (n=393 193 to n=461 460). Traits and biomarkers analyzed were body mass index, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein B, apolipoprotein A-I, C-reactive protein and vitamin D. Findings were then leveraged to build whole genome polygenic risk scores in participants from the Avon Longitudinal Study of Parents and Children (mean age, 9.9 years) which were used to stratify this cohort into deciles in turn and analyzed against their respective traits.
    Results: For each of the 10 different traits assessed, we found strong evidence of an incremental trend across deciles (all
    Conclusions: Although the use of polygenic prediction in a clinical setting may currently be premature, our findings suggest they are becoming increasingly powerful as a means of predicting complex trait variation at an early stage in the lifecourse.
    MeSH term(s) Biological Specimen Banks ; Biomarkers/blood ; Cardiometabolic Risk Factors ; Child ; Cohort Studies ; Female ; Genetic Variation ; Genome-Wide Association Study ; Humans ; Linear Models ; Linkage Disequilibrium ; Longitudinal Studies ; Male ; Multifactorial Inheritance ; United Kingdom
    Chemical Substances Biomarkers
    Language English
    Publishing date 2022-01-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.121.316650
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: A lifecourse mendelian randomization study highlights the long-term influence of childhood body size on later life heart structure.

    O'Nunain, Katie / Park, Chloe / Urquijo, Helena / Leyden, Genevieve M / Hughes, Alun D / Davey Smith, George / Richardson, Tom G

    PLoS biology

    2022  Volume 20, Issue 6, Page(s) e3001656

    Abstract: Children with obesity typically have larger left ventricular heart dimensions during adulthood. However, whether this is due to a persistent effect of adiposity extending into adulthood is challenging to disentangle due to confounding factors throughout ... ...

    Abstract Children with obesity typically have larger left ventricular heart dimensions during adulthood. However, whether this is due to a persistent effect of adiposity extending into adulthood is challenging to disentangle due to confounding factors throughout the lifecourse. We conducted a multivariable mendelian randomization (MR) study to separate the independent effects of childhood and adult body size on 4 magnetic resonance imaging (MRI) measures of heart structure and function in the UK Biobank (UKB) study. Strong evidence of a genetically predicted effect of childhood body size on all measures of adulthood heart structure was identified, which remained robust upon accounting for adult body size using a multivariable MR framework (e.g., left ventricular end-diastolic volume (LVEDV), Beta = 0.33, 95% confidence interval (CI) = 0.23 to 0.43, P = 4.6 × 10-10). Sensitivity analyses did not suggest that other lifecourse measures of body composition were responsible for these effects. Conversely, evidence of a genetically predicted effect of childhood body size on various other MRI-based measures, such as fat percentage in the liver (Beta = 0.14, 95% CI = 0.05 to 0.23, P = 0.002) and pancreas (Beta = 0.21, 95% CI = 0.10 to 0.33, P = 3.9 × 10-4), attenuated upon accounting for adult body size. Our findings suggest that childhood body size has a long-term (and potentially immutable) influence on heart structure in later life. In contrast, effects of childhood body size on other measures of adulthood organ size and fat percentage evaluated in this study are likely explained by the long-term consequence of remaining overweight throughout the lifecourse.
    MeSH term(s) Adiposity/genetics ; Adult ; Body Mass Index ; Body Size/genetics ; Child ; Genome-Wide Association Study ; Humans ; Mendelian Randomization Analysis ; Obesity
    Language English
    Publishing date 2022-06-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3001656
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book ; Online: A lifecourse mendelian randomization study highlights the long-term influence of childhood body size on later life heart structure

    O’Nunain, Katie / Park, Chloe / Urquijo, Helena / Leyden, Genevieve M. / Hughes, Alun D. / Davey Smith, George / Richardson, Tom G.

    PLoS Biol

    2022  

    Abstract: Children with obesity typically have larger left ventricular heart dimensions during adulthood. However, whether this is due to a persistent effect of adiposity extending into adulthood is challenging to disentangle due to confounding factors throughout ... ...

    Abstract Children with obesity typically have larger left ventricular heart dimensions during adulthood. However, whether this is due to a persistent effect of adiposity extending into adulthood is challenging to disentangle due to confounding factors throughout the lifecourse. We conducted a multivariable mendelian randomization (MR) study to separate the independent effects of childhood and adult body size on 4 magnetic resonance imaging (MRI) measures of heart structure and function in the UK Biobank (UKB) study. Strong evidence of a genetically predicted effect of childhood body size on all measures of adulthood heart structure was identified, which remained robust upon accounting for adult body size using a multivariable MR framework (e.g., left ventricular end-diastolic volume (LVEDV), Beta = 0.33, 95% confidence interval (CI) = 0.23 to 0.43, P = 4.6 × 10(−10)). Sensitivity analyses did not suggest that other lifecourse measures of body composition were responsible for these effects. Conversely, evidence of a genetically predicted effect of childhood body size on various other MRI-based measures, such as fat percentage in the liver (Beta = 0.14, 95% CI = 0.05 to 0.23, P = 0.002) and pancreas (Beta = 0.21, 95% CI = 0.10 to 0.33, P = 3.9 × 10(−4)), attenuated upon accounting for adult body size. Our findings suggest that childhood body size has a long-term (and potentially immutable) influence on heart structure in later life. In contrast, effects of childhood body size on other measures of adulthood organ size and fat percentage evaluated in this study are likely explained by the long-term consequence of remaining overweight throughout the lifecourse.
    Keywords Discovery Report
    Subject code 796
    Language English
    Publishing date 2022-06-09
    Publisher Public Library of Science
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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